Project 2: Racial/ethnic differences, impact on tumor microenvironment and mortality

项目2：种族/民族差异、对肿瘤微环境和死亡率的影响

• 批准号: 10044050
• 负责人: ULRIKE PETERS
• 金额: $ 32.4万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10044050
• 关键词: 16S ribosomal RNA sequencing; Address; African American; Age; Alaska Native; Animals; Archives; Bacteria; Bacteroides fragilis; Behavioral; Biological Assay; Cancer Control; Cancer Etiology; Colorectal; Colorectal Cancer; Colorectal Neoplasms; Communities; Consensus; Data; Development; Diet; Dietary Practices; Disease; Ensure; Environmental Exposure; Epithelial; Epithelium; Escherichia coli; Ethnic Origin; Ethnic group; Etiology; Fatty acid glycerol esters; Fiber; Fusobacterium nucleatum; Future; Gene Expression; Genomics; Goals; Health; Hispanics; Human; Immune; Incidence; Individual; Inflammation; Intervention; Lesion; Light; Link; Minority Groups; Native-Born; Natural History; Normal tissue morphology; Not Hispanic or Latino; Oncogenes; Outcome; Pathway interactions; Patients; Pattern; Persons; Play; Population; Population Group; Prevalence; Race; Reporting; Resources; Risk Factors; Role; Shoulder; Specimen; Structure; Suggestion; Time; Tissues; Tumor Biology; Tumor Burden; Tumor Tissue; United States; bacterial community; base; burden of illness; cancer diagnosis; cancer health disparity; cancer initiation; cancer subtypes; cancer survival; case control; colon cancer patients; colon tumorigenesis; colorectal cancer progression; colorectal cancer risk; design; digital; ethnic difference; ethnic diversity; fruits and vegetables; gut bacteria; gut microbiome; gut microbiota; microbial community; microbiome; microbiome components; microbiota; molecular subtypes; mortality; outcome forecast; polyketide synthase; premalignant; prognostic; racial and ethnic; racial and ethnic disparities; racial difference; sex; transcriptome sequencing; translational research program; tumor; tumor microbiome; tumor microenvironment; tumor progression

Project Summary/Abstract of Project 2 Colorectal cancer (CRC) incidence and mortality vary substantially by race/ethnicity in the United States (US). Alaska Natives have among the highest reported rates of CRC in the world; African Americans also shoulder an elevated burden from this disease compared to other groups within the US. In exploring factors that may contribute to these observed disparities, minimal consideration has been paid to the potential contribution of the microbiome. Although the presence of a gut microbial community is common across all human populations, the composition of that community varies greatly – by sex, diet, and race/ethnicity. The composition of the gut microbiome has plausible implications for a variety of pertinent health outcomes, including CRC. Increasing evidence indicates that specific gut bacteria, or imbalances in bacterial populations, could play a role in the natural history of CRC. For example, Fusobacterium nucleatum has been suggested to infiltrate the colorectal epithelium, promote CRC by increasing oncogene expression and inflammation, and contribute to poorer CRC survival. However, many questions remain as to the contributions of the microbiome to CRC across population groups, and the implications of those contributions. The objective of this study is to identify differences in the tumor-associated microbiome in CRC by race/ethnicity, associations of the tumor-associated microbiome with other aspects of the tumor microenvironment, and the impact on CRC survival. In Aim 1, we will assess differences in the bacterial community in CRC by race/ethnicity, focusing on both suspected candidate bacteria with plausible roles in CRC pathways (i.e., F. nucleatum, enterotoxigenic Bacteroides fragilis, and polyketide synthase-positive Escherichia coli – Aim 1a) and agnostic community-wide assays (Aim 1b). In Aim 2, we will examine how our evaluated candidate bacteria (2a) and agnostic patterns of bacterial community structure (2b) relate to prognostically-relevant gene-expression-based CRC subtypes and immune profiles in CRC tissue, considering possible differences by race/ethnicity. Lastly, in Aim 3, we will evaluate the relationship of suspected candidate bacteria (3a) and agnostic patterns of bacterial community structure (3b) with CRC survival, again considering possible differences in associations by race/ethnicity. In pursuit of these Aims, we will conduct targeted candidate (e.g., F. nucleatum-specific) and agnostic global assays (i.e., 16S rRNA gene sequencing) to characterize the bacterial community in CRC for 840 CRC cases from existing study resources with coverage of four racial/ethnic groups: Alaska Native people (n=210), African Americans (n=210), Hispanics (n=210), and non-Hispanic whites (n=210). Generating and contrasting information on the tumor- associated microbiome across racially/ethnically diverse groups, and relating all these data to CRC outcomes will provide an opportunity to advance our understanding of the microbiota’s role(s) in CRC health disparities. Information gained from this project will inform future strategies for targeted interventions and CRC control with the goal of reducing observed disparities in CRC incidence and mortality.

项目摘要/项目摘要